title: Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer.
abstract: BACKGROUND
  MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed.
  
  
  METHODS
  MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays.
  
  
  RESULTS
  Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay.
  
  
  CONCLUSIONS
  MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.
authors.affiliation: Department of Pathology, College of Medicine, CHA University, 351 Yatap-dong, Seongnam, Gyeonggi-Do, South Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Huh
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: J-A
authors.initials: JA
authors.lastname: Song
authors.forename: Y J
authors.initials: YJ
authors.lastname: Jung
authors.forename: J-Y
authors.initials: JY
authors.lastname: Jeong
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.forename: D H
authors.initials: DH
authors.lastname: Lee
authors.forename: H J
authors.initials: HJ
authors.lastname: An
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D046228:Microarray Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use*; D016019:Survival Analysis; D059467:Transcriptome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C542541:MIRN106 microRNA, human; C583766:MIRN591 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel